Table 4.
Parameter estimates for acute phase response dynamics and blood lymphocyte count
| Parameter (units) | Definition | Estimate (% CV) |
|---|---|---|
| Signal transducer and activator of transcription-3 mRNA and protein dynamics | ||
| kd,STAT3m (h−1) | Degradation rate constant for STAT3 mRNA | 0.33 (24.0) |
| Stimulation constant for STAT3 mRNA synthesis | 0.005 (10.9) | |
| kd,STAT3 (h−1) | Degradation rate constant for STAT3 protein | 0.12 (22.3) |
| γSTAT3 | Amplification factor for STAT3 protein | 1.9 (9.3) |
| kSTAT3 (h−1) | Phosphorylation/translocation rate constant | 4.16 (fixed) |
| STAT3m (0) | Baseline STAT3 mRNA | 1 (fixed) |
| STAT3 (0) | Baseline STAT3 protein | 1 (fixed) |
| Serpin A1n and serpin A3 protein dynamics | ||
| kd,SerpinA3n (h−1) | Degradation rate constant for serpin A3n | 1.4 (fixed) |
| λ1 | Power coefficient for pSTAT3N effect on serpin A3n | 1.5 (17.5) |
| kd,SerpinA1 (h−1) | Degradation rate constant for serpin A1 | 1.4 (fixed) |
| λ2 | Power coefficient for pSTAT3N effect on serpin A1 | 0.6 (20.9) |
| Serpin A3n (0) | Baseline SerpinA3n protein | 1 (fixed) |
| Serpin A1 (0) | Baseline SerpinA1 protein | 1 (fixed) |
| Blood lymphocyte dynamics | ||
| kin (h−1) | Trafficking rate constant for lymphocytes from tissue to blood | 0.002 (14.3) |
| kout (h−1) | Trafficking rate constant for lymphocytes from blood to tissue | 0.23 (5.0) |
| IC50, MPL (ng/mL) | Drug concentration inhibiting kin by 50% | 6.15 (fixed) |
| kapoptosis (nM−1h−1) | Second-order rate constant of LYMT apoptosis | 0.0019 (72.6) |
| β1 | Intrinsic efficiency of Serpin A1 | 1 (fixed) |
| β2 | Intrinsic efficiency of Serpin A3n | 1 (fixed) |
| LYMB (0) (K/uL) | Baseline blood lymphocyte count | 4.8 (fixed) |
| LYMT (0) (K/uL) | Baseline tissue lymphocyte count | 475.2 (fixed) |